Alitretinoin

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Alitretinoin
Alitretinoin2DACS.svg
Alitretinoin3Dan.gif
Systematic (IUPAC) name
(2E,4E,6Z,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-
1-cyclohexenyl)nona-2,4,6,8-tetraenoic acid
Clinical data
Trade names Panretin (gel), Toctino (oral)
AHFS/Drugs.com monograph
MedlinePlus a601012
Licence data EMA:Link, US FDA:link
Pregnancy
category
  • US: D (Evidence of risk)
Legal status
Routes of
administration		 Topical, oral
Pharmacokinetic data
Protein binding Highly bound, no exact figure available[1]
Metabolism Hepatic (CYP3A4-mediated oxidation, also isomerised to tretinoin)[1]
Biological half-life 2-10 hours[1]
Excretion Urine (64%), faeces (30%)[1]
Identifiers
CAS Number 5300-03-8 YesY
ATC code D11AH04 (WHO) L01XX22
PubChem CID: 449171
IUPHAR/BPS 2645
DrugBank DB00523 YesY
ChemSpider 395778 YesY
UNII 1UA8E65KDZ YesY
ChEBI CHEBI:50648 YesY
ChEMBL CHEMBL705 YesY
Chemical data
Formula C20H28O2
Molecular mass 300.435 g/mol
  • O=C(O)\C=C(\C=C\C=C(/C=C/C1=C(/CCCC1(C)C)C)C)C
  • InChI=1S/C20H28O2/c1-15(8-6-9-16(2)14-19(21)22)11-12-18-17(3)10-7-13-20(18,4)5/h6,8-9,11-12,14H,7,10,13H2,1-5H3,(H,21,22)/b9-6+,12-11+,15-8-,16-14+ YesY
  • Key:SHGAZHPCJJPHSC-ZVCIMWCZSA-N YesY
  (verify)

Alitretinoin, or 9-cis-retinoic acid, is a form of vitamin A. It is also used in medicine as an antineoplastic (anti-cancer) agent developed by Ligand Pharmaceuticals. It is a first generation retinoid. Ligand gained Food and Drug Administration (FDA) approval for alitretinoin in February 1999.

Medical uses

Kaposi’s sarcoma

In the United States, topical alitretinoin (in the form of a gel; trade name Panretin) is indicated for the treatment of skin lesions in AIDS-related Kaposi's sarcoma. Alitretinoin is not indicated when systemic therapy against Kaposi's sarcoma is required.[2] It has received EMA (11 October 2000) and FDA (2 March 1999) approval for this indication.[3][4]

Chronic hand eczema

Under the trade name Toctino (marketed by GSK, UK) it has been granted prescription rights in the UK (08/09/2008) for oral use in chronic hand eczema.[5] In May 2009 the National Institute for Health and Clinical Excellence (NICE) issued preliminary guidance[6] on the use of Alitretinoin for the treatment of severe chronic hand eczema in adults. The recommendation stated that only patients with severe chronic hand eczema who are unresponsive to potent topical corticosteroids, oral immunosuppressants or phototherapy should receive the drug. Final NICE guidance is expected in August 2009.

Adverse effects

Adverse effects by frequency

Systemic use, when being used to treat chronic hand eczema[1][4]

Very common (>10% frequency):

  • Headache
  • Hypertriglyceridemia
  • High density lipoprotein decreased
  • Hypercholesterolemia

Common (1-10% frequency):

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Uncommon (0.1-1% frequency):

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Rare (<0.1% frequency):

  • Benign intracranial hypertension

Unknown frequency:

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  • Anaphylactic reactions
  • Hypersensitivity
  • Depression
  • Mood changes
  • Suicidal ideation
  • Decreased night vision

Topical use for Kaposi's sarcoma[7]

Very common (>10% frequency):

Common (1-10% frequency):

Contraindications

Pregnancy is an absolute contraindication as with most other Vitamin A products, it should also be avoided when it comes to systemic use in any women that is of childbearing potential and not taking precautions to prevent pregnancy.[1] Toctino (the oral capsule formulation of alitretinoin) contains soya oil and sorbitol. Patients who are allergic to peanut, soya or with rare hereditary fructose intolerance should not take this medicine.[1] It is also contraindicated in nursing mothers.[1] The oral formulation of alitretinoin is contraindicated in patients with:[1]

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Interactions

It is a CYP3A4 substrate and hence any inhibitor or inducer of this enzyme may alter plasma levels of alitretinoin.[1] It should not be given to patients with excess vitamin A in their system as there is a potential for its actions on the retinoid X receptor to be exacerbated.[1] It may also interact with tetracyclines to cause benign intracranial hypertension.[1]

Overdose

Alitretinoin is a form of vitamin A. Alitretinoin has been administered in oncological clinical studies at dosages of more than 10-times of the therapeutic dosage given for chronic hand eczema. The adverse effects observed were consistent with retinoid toxicity, and included severe headache, diarrhoea, facial flushing and hypertriglyceridemia. These effects were reversible.[1]

Mechanism of action

Alitretinoin is believed to be the endogenous ligand (a substance that naturally occurs in the body that activates this receptor) for retinoid X receptor, but it also activates the retinoic acid receptor.[1][8][9]

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 Lua error in package.lua at line 80: module 'strict' not found.
  2. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  3. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  4. ↑ 4.0 4.1 Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  7. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  9. ↑ Lua error in package.lua at line 80: module 'strict' not found.

External links

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